ABSTRACT Despite the serious public health problem of obesity in older adults, the appropriate treatment approach for obese older adults remains highly controversial. A prevailing safety concern is that weight loss could cause further loss of bone mineral density (BMD) and increase the risk of bone fractures. Indeed, recent studies have shown that lifestyle therapy (diet plus exercise) resulting in weight loss in this understudied population improves physical function, cardiometabolic risk factors, and cognition, but a major complication appears to be loss of BMD. The addition of exercise to diet-induced weight loss attenuated but did not eliminate weight-loss- induced reduction of BMD. Previous studies, however, used dual-energy-x-ray-absorptiometry to monitor bone changes, which provides information on bone quantity but not bone quality. Bone quality refers to the material and structural properties of bone strength. The load-bearing capacity of a bone depends not only on the amount of bone but also on the spatial distribution and intrinsic properties of the materials that comprise the bone. Because of previous lack of options to assess bone quality in vivo, there has been little or no scientific study of the possibility that lifestyle change in obese older adults improves bone quality. Preliminary studies suggest that lifestyle therapy may improve bone quality despite reducing BMD by suppressing inflammation. This will be the first randomized controlled trial (RCT) in obese older adults to comprehensively examine the effects of lifestyle therapy on bone quality using state-of-the-art and novel techniques. One- hundred-twenty obese older adults will be randomized to 1 year of lifestyle intervention or healthy lifestyle (control) to test the following primary hypotheses: 1) lifestyle therapy will improve bone microarchitecture in obese older adults relative to a control condition, 2) lifestyle therapy will improve femoral bone strength in obese older adults relative to a control condition, and 3) lifestyle therapy will improve bone material strength in obese older adults relative to a control condition. The secondary hypothesis is that changes in the canonical Wnt signaling (? sclerostin, an inhibitor of bone formation during states of unloading) and noncanonical Wnt signaling (? Wnt5A/Sfrp5 and inflammation) may mediate the changes in bone quality during lifestyle therapy. The central hypothesis is that lifestyle intervention will be highly successful in obese older adults with resultant improvement in the material and structural properties of bone (i.e. bone quality) despite a reduction in BMD. The track record of the investigative team in lifestyle interventions in obese older adults, coupled with the Bone Imaging Core Resources at the Center for Translational Research on Inflammatory Diseases at Baylor College of Medicine and Michael E DeBakey VA Medical Center, represents an unprecedented opportunity to prove the hypothesis that lifestyle therapy improves bone quality in this population. The evidence-based data from this RCT should resolve the lingering controversy of whether lifestyle intervention is safe for bone health and thus overall beneficial, which will change clinical practice guidelines for obesity in older adults.